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FLASH GENE

Symbol

ID1

contributors: mct/pgu - updated : 15-12-2015

HGNC name	inhibitor of DNA binding 1, dominant negative helix-loop-helix protein
HGNC id	5360

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	20q11.21      Physical location : 30.193.091 - 30.194.313
Synonym name	inhibitor of differentiation 1
	DNA-binding protein inhibitor ID-1
	helix-loop-helix protein
Synonym symbol(s)	ID, bHLHb24, ID-1, dJ857M17.1.2

DNA

TYPE	functioning gene
STRUCTURE	1.22 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D20Z1 - ID1 - BCL2L7P1 ,E2F1 - GHRH - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002165 2 splicing 993 NP_002156 - 155 - 2001 11278321 isoform a NM_181353 1 splicing 1234 NP_851998 - 149 - 2001 11278321 isoform b

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol blood / hematopoietic thymus       highly Cardiovascular heart       highly Digestive liver       lowly Endocrine pancreas       highly Nervous brain       highly Reproductive male system prostate     highly Respiratory lung       highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic         Connective         Epithelial secretory glandular endocrine   Lymphoid

cells

System Cell Pubmed Species Stage Rna symbol   digestive Lymphoid/Immune B cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

cell cycle

cell cycle, interphase, G1

Text	during early development, in progenitor cells, and specifically detected in the epithelial cells of growing ductal structures during early pregnancy

PROTEIN

PHYSICAL PROPERTIES		basic
STRUCTURE

motifs/domains

basic helix-loop-helix (bHLH) domain

conjugated

ubiquitinated

mono polymer

heteromer , dimer

HOMOLOGY

interspecies	homolog to murine Id1 (94.6pc)
	homolog to rattus Id1 (92.6pc)

Homologene

FAMILY	helix loop helix family of proteins
	ID subfamily

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus

basic FUNCTION	transcriptional repressor of CDKN2A
	inhibiting transcription factors of the basic helix loop helix family
	acting as inhibitors of the basic helix-loop-helix (bHLH) transcription factors that control cell differentiation, development and carcinogenesis
	controlling growth and/or differentiation of several cell types (negatively)
	potentially required for neurogenesis and angiogenesis (inducing inactivation of p16 (INK4a)/pRB pathway
	involved in TGF beta 1 signaling pathway in active heterodimers with the b HLH transcription factors through their HLH motifs
	required for the mobilization of endothelial precursor cells from the bone marrow during pathological tumor angiogenesis, and its expression remains high in tumor neovasculature
	having tumor-initiating capacity to rare breast cancer cells within the more common types of breast tumors with high lung metastatic potential
	play an essential role in the regulation of breast epithelial cell differentiation and proliferation
	attenuates Notch signaling and impairs T-cell commitment by elevating DTX1 expression
	promotes expansion and survival of primary erythroid cells and is a target of JAK2V617F-STAT5 signaling
	inhibiting breast cancer cell grotwh through the upregulation of p21 gene expression via the interaction with ERBeta1
	ID1 and ID3 negatively regulate the transition from lineage-specified hemogenic cells to committed hematopoietic progenitors during hematopoiesis of both embryonic stem cells and induced pluripotent stem cell

CELLULAR PROCESS	cell life, differentiation
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

development

text	B-cell differentiation

PATHWAY

metabolism

signaling

signal transduction

TGF beta 1 signaling pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	interacting woth COPS5
	interacting with ERbeta1
	ARID3A is a binding partner for ID1 (shares structural similarities with ID1 and recently implicated in TGF-beta1 signaling during embryogenesis
	NR1D1 could also mediate repression via ID1 binding in the absence of heme
	regulated BMI1 transcription through MYC binding to its E-box in the promoter
	link between ID1 and PcG proteins and ID1 may contribute potentially to tumor development through PcG-mediated epigenetic regulation
	is a novel target of PRKCA signaling (PRKCA signaling regulates inhibitor of DNA binding 1 in the intestinal epithelium)
	SMURF2 is an E3 ligase that ubiquitinates ID1 and ID3 (SMURF2-mediated ubiquitination and consequent degradation of ID1 or ID3 plays an important role in the regulation of Id expression in senescent cells
	interaction with LARP6 (LARP6 may be an effective mediator of promoting endothelial proliferation, angiogenesis and wound healing probably by regulating VEGF together with ID1)

cell & other

REGULATION

induced by	tumors in enfothelial progenitors cells
		TGFBeta1

repressed by

ZBTB18, repressing ID1, ID2, ID3, ID4 genes during corticogenesis

Other

downregulated as cells differentiate into pre-B and mature B cells

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in gastric cancer tumoral     --over   in prostate cancer tissues tumoral         expression in androgen-dependent prostate cancer is negatively regulated by androgen through androgen-receptor tumoral         expression of mRNA in bone marrow and peripheral blood was significantly associated with lymph node metastasis and peritoneal dissemination in gastric carcinoma patients

Susceptibility

Variant & Polymorphism

Candidate gene	plays an important role in polycythemia vera
Marker
Therapy target
	System Type Disorder Pubmed cancer urinary   upregulation of ID1 in bladder cancer cells lead to increased cell viability in response to epirubicin and downregulation of Id1 increases cellular sensitivity to epirubicin by increased anticancer drug-induced apoptosis cancer reproductive breast peptide aptamer, Id1/3-PA7, specifically interacting with ID1 and ID3, could represent a nontoxic exogenous agent that can significantly provoke antiproliferative and apoptotic effects in breast cancer cells, which are associated with deregulated expressi

ANIMAL & CELL MODELS

combined Id1 and Id3 deletion leads to dysregulation of the hematopoietic transcriptional network and multiple defects in erythropoietic development in adult mice